硫化氢供体对阿霉素心肌病大鼠氧化应激作用的影响

目的： 探讨外源性给予硫化氢供体硫氢化钠(NaHS)对阿霉素(adriamycin, ADR)心肌病大鼠氧化应激作用的影响。方法：雄性Wistar大鼠54只，随机分为5组：(1) ADR组(n=12)：腹腔注射ADR，每次2.5 mg/kg，每周1次，共用药10周；(2)ADR+小剂量NaHS组（n=12）：ADR用药方法同ADR组，同时经腹腔注射NaHS，2.8 μmol·kg-1·d-1，连续用药10周；(3)ADR+大剂量NaHS组（n=12）：ADR用药方法同ADR组，同时经腹腔注射NaHS，14 μmol·kg-1·d-1，连续用药10周；(4)对照组（n=9）：用相同容量的生理盐水代替ADR，给药方法同ADR组；(5)NaHS组（n=9）：经腹腔注射NaHS，14 μmol·kg-1·d-1，连续用药10周。于第10周检测大鼠心功能和血流动力学指标,并测定其血清及心肌组织中H2S、脂质过氧化物丙二醛(MDA) 的含量以及超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)的活性，比较其中的差异。结果：ADR组大鼠心功能较对照组明显降低(均P<0.01)，且血清及心肌组织H2S含量均明显低于对照组(P<0.01），MDA含量明显较对照组升高(均P<0.01)，SOD的活性明显降低(均P<0.01)，GSH-Px的活性亦明显降低(血清及心肌组织：P<0.05，P<0.01)；经外源性补充H2S供体NaHS后，大鼠心功能较前明显改善，ADR+大剂量NaHS组心肌组织中过氧化产物MDA含量明显降低(均P<0.01)，而血清MDA含量无明显差异(P>0.05)；ADR+大剂量NaHS组血清SOD活性明显升高(P<0.01)，而心肌组织SOD活性无明显差异(P>0.05)；ADR+大剂量NaHS组心肌组织GSH-Px活性明显增高(均P<0.05)，而血清GSH-Px活性无明显差异(P>0.05)。结论：硫化氢参与了大鼠阿霉素心肌病的发病过程,外源性补充硫化氢供体NaHS可以改善阿霉素心肌病大鼠心功能，降低心肌组织中脂质过氧化物的含量，显著提高抗氧化酶体系的活性，减轻氧化应激损伤，从而参与对大鼠心肌的保护机制。

Effect of hydrogen sulfide donor on oxidative stress of myocardium in adriamycin-induced dilated cardiomyopathy rats

AIM: To investigate the effect of hydrogen sulfide (H2S) donor (NAHS) on oxidative stress of adriamycin-induced dilated cardiomyopathy rats. METHODS: Weight-matched adult male Wistar rats were randomly divided into 5 groups as follows: (1) ADR group (n=12), in which 2.5 mg/kg of adriamycin was injected intraperitoneally once a week for 10 weeks (total dose of 25 mg/kg). (2) ADR+small-dose NaHS group (n=12), in which the dosage and the use of adriamycin were as mentioned above, while NaHS solution was injected to rats at a dosage of 2.8 μmol·kg-1·d-1 at the same time. (3) ADR + large-dose NaHS group (n=12), in which the dosage and the use of adriamycin were as mentioned above, while NaHS solution was injected to rats at a dosage of 14 μmol·kg-1·d-1 at the same time. (4) Control group (n=9), in which an equivalent volume of physiological saline was administered weekly for a total of 10 weeks. (5) NaHS group (n=9), in which 14 μmol/kg of NaHS solution was injected to rats intraperitonealy once a week for 10 weeks. Hemodynamic and echocardiographic measurements were obtained 10 weeks after the treatment. Meanwhile, H2S and malondialdehyde (MDA) concentrations, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in serum and myocardial tissues were evaluated, respectively. RESULTS: The cardiac functions in the group of ADR rats depressed obviously. H2S concentrations, SOD and GSH-Px activities in serum and myocardial tissues of ADR group rats were all significantly decreased as compared with those in the control group (P<0.01). The MDA concentrations in serum and myocardial tissues in ADR group rats were both increased significantly (P<0.01). Exogenous administration of H2S donor NaHS markedly attenuated ADR-induced cardiac dysfunction, and MDA concentration in myocardial tissues was significantly reduced (P<0.01). Serum SOD activity was obviously increased in ADR+large-dose NaHS group compared with control group (P<0.01), and GSH-Px activity in myocardial tissues was markedly increased in ADR+large-dose NaHS group compared with control group (P<0.05). CONCLUSION: H2S might play an important role in the development of adriamycin-induced dilated cardiomyopathy. Administration of exogenous H2S effectively improves myocardial contractile activity, reduces the accumulation of lipid peroxides and increases the capability of antioxidants to inhibit oxidative stress and prevents myocardial damage.